A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials

Zafereo, Mark; McIver, Bryan; Vargas-Salas, Sergio; Domínguez, José Miguel; Steward, David L.; Holsinger, F. Christopher; Kandil, Emad; Williams, Michelle D.; Cruz, Francisco; Loyola, Soledad; Solar, Antonieta; Roa, Juan Carlos; León, Augusto; Droppelman, Nicolás; Lobos, Maite; Arias, Tatiana; Kong, Christina S.; Busaidy, Naifa L.; Grubbs, Elizabeth G.; Graham, Paul H.; Stewart, John; Tang, Alice; Wang, Jiang; Orloff, Lisa A.; Henríquez, Marcela P.; Lagos, Marcela; Osorio, M Jaime; Schachter, Dina; Franco, Carmen; Medina, Francisco J.; Wohllk, Nelson; Díaz, R.; Véliz, Jesús; Horvath, Eleonora; Tala, Hernán; Pineda, Pedro; Arroyo, Patricia; Vasquez, Felix; Traipe, E; Marín, Luis; Miranda, Giovanna F.; Bruce, Elsa; Bracamonte, Milagros Sierra; Mena, Natalia; González, Hernán

doi:10.1089/thy.2019.0490

Cited by 19 publications

(15 citation statements)

References 21 publications

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“…This type of testing takes a different approach from that of ThyroSeq v3 and Veracyte Afirma which require the original institution to submit the sample for molecular testing to centralized laboratories. Recent independent studies of international cohorts reported NPVs of 96% and 94%, which would be acceptable as "rule out" tests (36). However, additional independent studies for the 10gene panel (thyroid genetic classifier) with detailed performance characteristics and cost comparisons to the other molecular panels would be of interest.…”

Section: Molecular Testingmentioning

confidence: 99%

Molecular testing and thyroid nodule management in North America

Ohori

2020

Gland Surg

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The incidence of thyroid cancer is rising for a variety of reasons. At the same time, the nomenclature revision of non-invasive encapsulated follicular-variant PTC to noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) has modified the incidence of thyroid cancer. Given that thyroid neoplasia is a molecular event, it is important for the thyroid physician to evaluate each patient systematically. Most thyroid cancers are sporadic; however, some are familial and may be associated with syndromes with genetic implications. Advances in radiologic imaging have made ultrasonography a near equivalent of gross examination. The American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) classifies nodules from TR1 to TR5 and is valuable in determining which patients should be guided toward fine-needle aspiration (FNA) sampling. While FNA procedures and processing may be varied, the key elements are cytologic diagnosis and collection of samples for potential molecular testing. The Bethesda System for Reporting Thyroid Cytology (BSRTC) is commonly used and categorizes each FNA specimen into one of six diagnoses. The indeterminate diagnoses with risk of malignancy (ROM) ranging from 10-75% comprise approximately 30% of thyroid FNA cases and for these, molecular testing is beneficial. In North America, the two most common molecular platforms are Veracyte Afirma GSC and ThyroSeq v3. Both panels cover an extensive array of genomic alterations associated with thyroid neoplasia and a negative result from either test effectively refines the ROM of an Atypia of Undetermined Significance/ Follicular Lesion of Undetermined Significance (AUS/FLUS) or Follicular Neoplasm/Suspicious for a Follicular Neoplasm (FN/SFN) diagnosis to 3-4%. Given that the refined ROMs are comparable to that of a Benign BSRTC diagnosis, these patients are recommended for observation of their nodules. However, differences exist in the implication of Afirma GSC-Suspicious and ThyroSeq v3-Positive molecular results with regard to the probability of cancer. For either test, the molecular test result should be integrated with other clinical parameters to determine if surgery is indicated and, if so, the extent of surgery.

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Section: Molecular Testingmentioning

confidence: 99%

Molecular testing and thyroid nodule management in North America

Ohori

2020

Gland Surg

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“…On average, 15%-25% of the nodules with indeterminate cytology that are operated on are malignant. About 60% of them are PTC, of which up to 10% require totalization (28)(29)(30). Between 10%-15% are FTC; information on indication to totalization is scarce in this setting (27,28).…”

Section: Discussionmentioning

confidence: 99%

Clinical and histopathological features of follicular thyroid cancer in Chile

Díaz¹,

Domínguez²,

Tala³

et al. 2023

Archives of Endocrinology and Metabolism

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Objective: Follicular thyroid carcinoma (FTC) is less frequent but has a worse prognosis than papillary carcinoma. The available evidence on pre-operative characteristics of FTC is controversial. Our objective was to characterize the clinical, ultrasound and histopathological presentation of FTC patients treated Chile. Subjects and methods: Retrospective analysis of 97 patients treated for FTC in 6 large centers in Chile. We analyzed their ultrasonographic features and classified the nodules according to ATA risk of malignancy and TI-RADS score, as well as the cytological findings according to the Bethesda system. We described their clinical and histopathological findings at diagnosis and classified their risk of recurrence and mortality according to ATA 2015 recurrence risk category and the eighth edition of the AJCC/UICC staging system, respectively. Results: Median age was 48 years and 73.2% were females. The median diameter was 38.8 mm; only 9.5% of them were microtumors. According to ATA risk of malignancy, 86% of the nodules were low or intermediate suspicious, while 78% were category 3 or 4A nodules according to the TI-RADS. Regarding the Bethesda system, 65.9% had indeterminate cytology (20.6% category III and 45.3% category IV). At histological examination, most were minimally-invasive and angio-invasive tumors with less than 4 foci (54.7% and 28.4% respectively). More than 90% of FTC were unifocal and there was no lymphovascular or extrathyroidal invasion or lymph node involvement. Four patients (4.1%) had distant metastases at diagnosis. Most patients (95%) had stage I or II disease according to the AJCC/UICC staging system, while the risk of recurrence was low at 51.5% when using the ATA risk of recurrence scale. Conclusions: At diagnosis, most FTCs were nodules of low or intermediate suspicion at ultrasound, nearly two thirds had indeterminate cytology according to the Bethesda system, and nearly 50% of them were of low risk of recurrence.

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“…4,5,12,13 Some of these tests are now being used routinely in clinical practice, particularly in the United States, to rule out malignancy claiming false negative rates similar to that of benign cytology. [14][15][16][17][18] However, the predictive values of any diagnostic test are influenced by the pretest risk of malignancy. 19 Therefore, clinical, radiological and cytological information that precedes the molecular test needs to be considered for the indication and correct interpretation of the molecular test's results.…”

Section: Molecular Tests For the Evaluation Of Cytologically Indeterm...mentioning

confidence: 99%

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer

Valderrábano

Eszlinger

Stewardson

et al. 2023

Clinical Endocrinology

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Objective Advances in our understanding of the molecular biology of thyroid tumours is being rapidly translated into their clinical management. This review summarizes the current use of molecular testing in thyroid tumours, focusing on their usefulness as diagnostic and prognostic tools to guide treatment with consideration of present limitations. Design Considerations about molecular testing applications for the diagnosis and treatment of thyroid tumours are divided into four sections/roles: (1) evaluating cytologically indeterminate thyroid nodules; (2) guiding extent of surgery in indeterminate thyroid nodules; (3) completing histological characterization of thyroid tumours and (4) identifying actionable mutations in advanced progressive thyroid cancers. Results Genomic testing can improve the presurgical malignancy risk assessment in indeterminate thyroid nodules. However, a prior in‐depth analysis of institutional quality and outcomes of sonographical, cytological and histological characterization of thyroid tumours is necessary. Presently, it remains uncertain whether knowing the molecular profile of a cytologically indeterminate thyroid nodule might be advantageous to modify the extent of initial surgery. Molecular characterization of thyroid tumours can be a valuable adjunct to morphological diagnosis in some challenging cases, such as in low‐risk follicular cell‐derived neoplasms, or rare tumours. Finally, as selective kinase inhibitors are available, molecular testing in locally advanced/metastatic progressive thyroid cancers should also be integrated into the institutional clinical management pathway to improve outcomes and limit toxicity. Conclusions Molecular testing needs to be implemented into the local evidence‐based clinical management thyroid nodule/cancer pathways to improve its diagnostic and prognostic value and to optimize cost‐effectiveness.

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A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials

Cited by 19 publications

References 21 publications

Molecular testing and thyroid nodule management in North America

Molecular testing and thyroid nodule management in North America

Clinical and histopathological features of follicular thyroid cancer in Chile

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer

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